title: Systematic review: impact of non-adherence to 5-aminosalicylic acid products on the frequency and cost of ulcerative colitis flares.
abstract: BACKGROUND
  Ulcerative colitis (UC) can be maintained in remission with 5-aminosalicylic acid (5-ASA) medications, but frequent non-adherence by patients who are feeling well has been associated with more frequent flares of colitis.
  
  
  OBJECTIVE
  To perform a systematic review of the published literature and unpublished randomized clinical trials (RCTs) regarding the impact of non-adherence with 5-ASA medications on the incidence of UC flares and costs of care.
  
  
  METHODS
  A search of MEDLINE, EMBASE and the Cochrane databases was performed. Prospective studies of UC maintenance with 5-ASAs in adults were selected if they included data on adherence and disease flares. Studies using insurance claims data to estimate the impact of non-adherence on cost of care were included. Data from unpublished RCTs were obtained from the FDA with a request under the Freedom of Information Act.
  
  
  RESULTS
  The relative risk for flare in non-adherent vs. adherent patients ranged from 3.65 to infinity. Data were obtained from six unpublished 5-ASA RCTs, but none measured the impact of adherence on disease activity. The comorbidity-adjusted annual costs of care in adherent patients were 12.5% less than in non-adherent patients, despite increased medication expenditures.
  
  
  CONCLUSIONS
  A substantial proportion of UC flares and medical costs of UC are attributable to 5-ASA non-adherence. As non-adherence to 5-ASA medications is common, cost-effective strategies to improve adherence are needed. The impact of adherence on disease activity should be measured in RCTs of all inflammatory bowel disease treatments.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA. phiggins@umich.edu
authors.forename: P D R
authors.initials: PD
authors.lastname: Higgins
authors.forename: D T
authors.initials: DT
authors.lastname: Rubin
authors.forename: K
authors.initials: K
authors.lastname: Kaulback
authors.forename: P S
authors.initials: PS
authors.lastname: Schoenfield
authors.forename: S V
authors.initials: SV
authors.lastname: Kane
mesh_terms: D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000191:economics; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000191:economics / Q000523:psychology; D003362:Cost-Benefit Analysis; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D019804:Mesalamine / Q000008:administration & dosage* / Q000191:economics; D008875:Middle Aged; D010349:Patient Compliance / Q000523:psychology / Q000706:statistics & numerical data*; D016032:Randomized Controlled Trials as Topic; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D019804:Mesalamine